title: The PARK2 gene is involved in the maintenance of pancreatic β-cell functions related to insulin production and secretion.
abstract: Several association studies have implicated the PARK2 gene that encodes parkin--the key molecule orchestrating the mitochondrial quality control system--as a candidate susceptibility gene for diabetes. A total of 7551 unrelated Korean KARE cohort subjects were analyzed to investigate the association between the PARK2 single nucleotide polymorphism (SNP) and quantitative glycemic traits. Two SNPs, rs10455889 and rs9365294, were significantly associated with fasting plasma glucose level (p=∼1.2×10(-4)) and insulin secretion indices (p=∼7.4×10(-5)) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 β-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted β-cells also exhibited increased mitochondrial fragmentation and ROS production and decreased mitochondrial membrane potential. Both population-based statistical evaluation and experimental evidence demonstrated a fundamental role of the PARK2 gene in the maintenance of β-cell function.
authors.affiliation: Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Jin
authors.affiliation: Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jeonghyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Statistics, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Kyunga
authors.initials: K
authors.lastname: Kim
authors.affiliation: Centre for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Go
authors.affiliation: Centre for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Metabolic Diseases, Centre for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Hye-Ja
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Metabolic Diseases, Centre for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
authors.forename: Byeong Tak
authors.initials: BT
authors.lastname: Jeon
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.affiliation: Drug Evaluation Centre, CJ CheilJedang Corporation, Icheon, Republic of Korea.
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Division of Epidemiology and Health Index, Centre for Genome Science, Korea Centres for Disease Control & Prevention, Chungcheongbuk-do, Republic of Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Hong
authors.affiliation: Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Centre, College of Medicine, Dong-A University, Republic of Korea.
authors.forename: Young-Hyun
authors.initials: YH
authors.lastname: Yoo
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Beomseok
authors.initials: B
authors.lastname: Oh
authors.affiliation: Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: kangy@ajou.ac.kr.
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: jeongsy@ajou.ac.kr.
authors.forename: Seon-Yong
authors.initials: SY
authors.lastname: Jeong
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D015331:Cohort Studies; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D007328:Insulin; D000255:Adenosine Triphosphate; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Genetic association; Insulin secretion; Mitochondria; PARK2; Pancreatic β-cell; Type 2 diabetes